Conditioned Open-label Placebos to Facilitate Opioid Reduction in Patients With Chronic Non-cancer Pain

NCT06350786 | Recruiting DMC

• 2 other identifiers: ROM StudyPZ00P1_201972
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate whether the reduction of the daily morphine equivalent dose (MED) in patients with chronic non-cancer pain (CNCP) can be decreased with an open-label placebo (OLP) intervention in comparison to an electronic monitoring (EM) control group. The participants will receive the intervention (OPL or EM) over the duration of six weeks. Diverse psychological and health measures will be assessed with questionnaires over the course of the intervention. Furthermore, evaluation outcomes, qualitative outcomes and safety outcomes will be assessed. It is hypothesized that the OLP-intervention group in comparison to the EM-control group will have a significantly lower consumption of MED over the course of the study. Furthermore, this study aims to evaluate whether the OLP intervention can reduce opioid withdrawal symptoms in comparison to the control group.

Conditions

Chronic Non-cancer Pain

Outcome Measures

Primary Outcomes (1)

• Daily opioid consumption (MED):

  Cumulative dose (i.e. total amount) of opioid pain medication consumption based on daily morphine equivalent doses (MED). Data is collected in SEMA3 app.

  Daily measure: starts on day 1 after the first intervention visit (baseline, day 0) after randomization and ends on day 42 at the end of the study.

Secondary Outcomes (10)

• Subjective opioid withdrawal symptoms

  Measured three times: on day 0 at the first intervention visit (baseline), on day 7, and on day 42 at the end of the study.

• Pain severity

  Measured three times: on day 0 at the first intervention visit (baseline), on day 7, and at the end of the study on day 42.

• Pain disability

  Measured three times: on day 0 at the first intervention visit (baseline), on day 7, and at the end of the study on day 42.

• Anxiety

  Measured three times: on day 0 at the first intervention visit (baseline), on day 7, and at the end of the study on day 42.

• Depression

  Measured three times: on day 0 at the first intervention visit (baseline), on day 7, and at the end of the study on day 42.

Other Outcomes (8)

• Rationale credibility

  One-time assessment: measured on day 42 at the end of the study.

• Placebo understanding

  One-time assessment: measured on day 42 at the end of the study.

• Patient Provider Connection

  One-time assessment: measured on day 42 at the end of the study.

Study Arms (2)

Open-Label Placebo

EXPERIMENTAL

The intervention involves administering "P-Dragees blue Lichtenstein," blue placebo pills devoid of active ingredients. Each pill contains lactose monohydrate; magnesium stearate (Ph. Eur.); microcrystalline cellulose; sucrose; glucose syrup; corn-starch; highly dispersed silicon dioxide; white clay; macrogol glycerol hydroxy stearate (Ph. Eur.); Gum arabic; montanglycol wax; povidone (K 25); talcum; titanium dioxide (E 171); calcium carbonate; macrogol 6000; patent blue V; aluminium salt (E 131). Participants will be informed that the pills are placebos and will be instructed to pair them with opioid medication for 7 days. After 7 days until the end of the study they will be instructed to continue to pair their opioid medication with an OLP pill and take additionally placebo pills on the basis of their need. An evidence-based rationale will be provided, explaining why the placebo treatment is deemed effective for pain. This rationale will precede the OLP intake procedure.

Other: P-Dragees blue Lichtenstein, Placebo dragees

Electronic monitoring (EM) control group

OTHER

EM is a method to objectively measure adherence and serves as the primary intervention component on the basis of which adherence trajectories will be discussed. The participants in the EM control group will receive an evidence-based rational designed to foster positive expectations and will be instructed on the mechanisms of EM. The EM control group is structurally equivalent to the OLP group referring to the number and duration of contacts between participants and the study team members as well as to the format of the intervention and the quality of the interaction.

Other: Control group (EM)

Interventions

P-Dragees blue Lichtenstein, Placebo dragees OTHER

In the intervention group, open-label placebos are administered within the framework of a mind-body management intervention approach, which in turn is consistent with the biopsychosocial model of pain and with a patient-centred approach. The verbal interaction follows the four discussion points: 1. Opioids work by telling the body that participants are not experiencing as much pain; 2. Placebos should be taken every time an opioid is taken which supports the reduction of opioid medication (shown by previous studies); 3. By pairing the pills together the brain will learn to release chemicals like endorphins that cause pain-relief in response to the placebo, just as it does in response to the opioid; 4. At a certain point, placebos might provide adequate pain relief, and the participants might need less opioids.

Open-Label Placebo

Control group (EM) OTHER

In the EM control group, the focus lies on the electronic monitoring (EM) of the opioid intake. The treatment rationale is designed to facilitate the reduction of opioid medication by promoting a positive attitude towards the implementation of the reduction. The verbal interaction follows the four discussion points: 1. The collection of EM data allows for greater patients' sense of agency over medication treatment; 2. Tracking of opioid medication use supports the reduction of opioid medication (shown by previous studies); 3. The EM is a useful tool, and daily recording of opioid medication intake should be done; 4. At a certain point, EM might provide adequate pain relief, and participants might need less opioids.

Electronic monitoring (EM) control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent
• ≥ 18 years of age
• German speaking
• Chronic non-cancer pain ≥ 6 months in duration
• Chronic opioid medication for \> 3 months
• Oral intake of opioid medication
• Motivation for opioid reduction
• Participants have a primary treating physician who performs the reduction of the opioid medication
• Having access to a computer or tablet with an email-account

You may not qualify if:

• Having psychotic symptoms
• Suicidality
• Cognitive impairment to everyday life
• Planned surgery within the next two months
• Known illegal drug or harmful alcohol consumption
• Intolerance of the ingredients of the placebo pill (e.g., lactose, sucrose, corn-starch)
• Serious health problems that make study participation impossible
• Simultaneous participation in other studies with investigational drugs or CNCP specific interventions

Sponsors & Collaborators

• Cosima Locher: lead
• Brown University: collaborator
• University of Basel: collaborator

Study Sites (1)

University Hospital Zurich, Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine

Zurich, Canton of Zurich, 8006, Switzerland

RECRUITING

Related Publications (8)

• Buergler S, Sezer D, Gaab J, Locher C. The roles of expectation, comparator, administration route, and population in open-label placebo effects: a network meta-analysis. Sci Rep. 2023 Jul 22;13(1):11827. doi: 10.1038/s41598-023-39123-4.

  PMID: 37481686 BACKGROUND

• Belcher AM, Cole TO, Massey E, Billing AS, Wagner M, Wooten W, Epstein DH, Hoag SW, Wickwire EM, Greenblatt AD, Colloca L, Rotrosen J, Magder L, Weintraub E, Wish ED, Kaptchuk TJ. Effectiveness of Conditioned Open-label Placebo With Methadone in Treatment of Opioid Use Disorder: A Randomized Clinical Trial. JAMA Netw Open. 2023 Apr 3;6(4):e237099. doi: 10.1001/jamanetworkopen.2023.7099.

  PMID: 37043203 BACKGROUND

• Bernstein MH, Magill M, Weiss AP, Kaptchuk TJ, Blease C, Kirsch I, Rich JD, Becker SJ, Mach S, Beaudoin FL. Are Conditioned Open Placebos Feasible as an Adjunctive Treatment to Opioids? Results from a Single-Group Dose-Extender Pilot Study with Acute Pain Patients. Psychother Psychosom. 2019;88(6):380-382. doi: 10.1159/000503038. Epub 2019 Sep 27. No abstract available.

  PMID: 31563914 BACKGROUND

• Estudillo-Guerra MA, Mesia-Toledo I, Schneider JC, Morales-Quezada L. The Use of Conditioning Open-Label Placebo in Opioid Dose Reduction: A Case Report and Literature Review. Front Pain Res (Lausanne). 2021 Jul 12;2:697475. doi: 10.3389/fpain.2021.697475. eCollection 2021.

  PMID: 35295534 BACKGROUND

• Flowers KM, Patton ME, Hruschak VJ, Fields KG, Schwartz E, Zeballos J, Kang JD, Edwards RR, Kaptchuk TJ, Schreiber KL. Conditioned open-label placebo for opioid reduction after spine surgery: a randomized controlled trial. Pain. 2021 Jun 1;162(6):1828-1839. doi: 10.1097/j.pain.0000000000002185.

  PMID: 33449503 BACKGROUND

• Morales-Quezada L, Mesia-Toledo I, Estudillo-Guerra A, O'Connor KC, Schneider JC, Sohn DJ, Crandell DM, Kaptchuk T, Zafonte R. Conditioning open-label placebo: a pilot pharmacobehavioral approach for opioid dose reduction and pain control. Pain Rep. 2020 Jul 20;5(4):e828. doi: 10.1097/PR9.0000000000000828. eCollection 2020 Jul-Aug.

  PMID: 32766465 BACKGROUND

• Sezer D, de Leeuw M, Netzer C, Dieterle M, Meyer A, Buergler S, Locher C, Ruppen W, Gaab J, Schneider T. Open-Label Placebo Treatment for Acute Postoperative Pain (OLP-POP Study): Study Protocol of a Randomized Controlled Trial. Front Med (Lausanne). 2021 Nov 5;8:687398. doi: 10.3389/fmed.2021.687398. eCollection 2021.

  PMID: 34805194 BACKGROUND

• Carratta K, Bodonyi K, Frey Nascimento A, Friis D, von Kanel R, Bircher L, Koechlin H, Bernstein M, Streitberger K, Arnet I, Roth AJ, Ronel J, Olliges E, Locher C. Conditioned open-label placebos to facilitate opioid reduction in patients with chronic non-cancer pain: study protocol of a randomised controlled trial. BMJ Open. 2025 May 24;15(5):e098253. doi: 10.1136/bmjopen-2024-098253.

  PMID: 40413049 DERIVED

MeSH Terms

Interventions

Control Groups

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Officials

• Cosima Locher, PhD

  USZ

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cosima Locher, PhD

CONTACT

+41 44 255 12 03; Cosima.Locher@usz.ch

Kiara Bodonyi, MSc

CONTACT

+41 44 255 14 24; Kiara.Bodonyi@usz.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 14, 2024
• First Posted: April 5, 2024
• Study Start: June 12, 2024
• Primary Completion: May 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: April 22, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 6 months after publication
• Access Criteria: Researchers with a methodologically sound proposal

Locations

CH (1)